Abstract：
N-acetylcysteine infusions have been widely used to reduce ischemia/reperfusion damage to the liver; however, convincing evidence of their benefits is lacking.
To perform the largest randomized controlled trial to compare the impact of N-acetylcysteine infusion during liver procurement on liver transplant outcomes.
Single center, randomized trial with patients recruited from La Fe University Hospital, Spain, from February 2012 to January 2016. A total of 214 grafts were transplanted and randomized to the N-acetylcysteine group (n = 113) or to the standard protocol without N-acetylcysteine (n = 101). The primary endpoint was allograft dysfunction (Olthoff criteria). Secondary outcomes included metabolomic biomarkers of oxidative stress levels, interactions between cold ischemia time and alanine aminotransferase level and graft and patient survival (ID no. NCT01866644).
The incidence of primary dysfunction was 34% (31% in the N-acetylcysteine group and 37.4% in the control group [P = 0.38]). N-acetylcysteine administration reduced the alanine aminotransferase level when cold ischemia time was longer than 6 h (P = 0.0125). Oxidative metabolites (glutathione/oxidized glutathione and ophthalmic acid) were similar in both groups (P > 0.05). Graft and patient survival rates at 12 mo and 3 y were similar between groups (P = 0.54 and P = 0.69, respectively).
N-acetylcysteine administration during liver procurement does not improve early allograft dysfunction according to the Olthoff classification. However, when cold ischemia time is longer than 6 h, N-acetylcysteine improves postoperative ALT levels.
To perform the largest randomized controlled trial to compare the impact of N-acetylcysteine infusion during liver procurement on liver transplant outcomes.
Single center, randomized trial with patients recruited from La Fe University Hospital, Spain, from February 2012 to January 2016. A total of 214 grafts were transplanted and randomized to the N-acetylcysteine group (n = 113) or to the standard protocol without N-acetylcysteine (n = 101). The primary endpoint was allograft dysfunction (Olthoff criteria). Secondary outcomes included metabolomic biomarkers of oxidative stress levels, interactions between cold ischemia time and alanine aminotransferase level and graft and patient survival (ID no. NCT01866644).
The incidence of primary dysfunction was 34% (31% in the N-acetylcysteine group and 37.4% in the control group [P = 0.38]). N-acetylcysteine administration reduced the alanine aminotransferase level when cold ischemia time was longer than 6 h (P = 0.0125). Oxidative metabolites (glutathione/oxidized glutathione and ophthalmic acid) were similar in both groups (P > 0.05). Graft and patient survival rates at 12 mo and 3 y were similar between groups (P = 0.54 and P = 0.69, respectively).
N-acetylcysteine administration during liver procurement does not improve early allograft dysfunction according to the Olthoff classification. However, when cold ischemia time is longer than 6 h, N-acetylcysteine improves postoperative ALT levels.
摘要：
N-乙酰半胱氨酸输注已被广泛用于减少肝脏的缺血/再灌注损伤；然而，缺乏令人信服的证据证明他们的好处。
进行最大的随机对照试验，以比较肝脏获取期间输注N-乙酰半胱氨酸对肝移植结果的影响。
单中心，从拉菲大学医院招募的患者的随机试验，西班牙,从2012年2月到2016年1月。总共移植了214个移植物，并随机分配到N-乙酰半胱氨酸组（n=113）或无N-乙酰半胱氨酸的标准方案（n=101）。主要终点是同种异体移植功能障碍（Olthoff标准）。次要结果包括氧化应激水平的代谢组学生物标志物，冷缺血时间和丙氨酸转氨酶水平与移植物和患者存活之间的相互作用（ID号NCT01866644)。
原发性功能障碍的发生率为34％（N-乙酰半胱氨酸组为31％，对照组为37.4％[P=0.38]）。冷缺血时间大于6h时，N-乙酰半胱氨酸可降低丙氨酸转氨酶水平（P=0.0125）。两组的氧化代谢产物(谷胱甘肽/氧化谷胱甘肽和眼酸)相似(P>0.05)。12个月和3个月的移植物和患者生存率在组间相似（分别为P=0.54和P=0.69）。
根据Olthoff分类，肝脏获取期间的N-乙酰半胱氨酸给药不能改善早期同种异体移植功能障碍。然而,当冷缺血时间超过6小时时，N-乙酰半胱氨酸可改善术后ALT水平。
进行最大的随机对照试验，以比较肝脏获取期间输注N-乙酰半胱氨酸对肝移植结果的影响。
单中心，从拉菲大学医院招募的患者的随机试验，西班牙,从2012年2月到2016年1月。总共移植了214个移植物，并随机分配到N-乙酰半胱氨酸组（n=113）或无N-乙酰半胱氨酸的标准方案（n=101）。主要终点是同种异体移植功能障碍（Olthoff标准）。次要结果包括氧化应激水平的代谢组学生物标志物，冷缺血时间和丙氨酸转氨酶水平与移植物和患者存活之间的相互作用（ID号NCT01866644)。
原发性功能障碍的发生率为34％（N-乙酰半胱氨酸组为31％，对照组为37.4％[P=0.38]）。冷缺血时间大于6h时，N-乙酰半胱氨酸可降低丙氨酸转氨酶水平（P=0.0125）。两组的氧化代谢产物(谷胱甘肽/氧化谷胱甘肽和眼酸)相似(P>0.05)。12个月和3个月的移植物和患者生存率在组间相似（分别为P=0.54和P=0.69）。
根据Olthoff分类，肝脏获取期间的N-乙酰半胱氨酸给药不能改善早期同种异体移植功能障碍。然而,当冷缺血时间超过6小时时，N-乙酰半胱氨酸可改善术后ALT水平。
